Gene Therapy of Human Breast Cancer.
Annual rept. 1 Oct 94-30 Sep 95,
MICHIGAN UNIV ANN ARBOR
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The adenoviral vector expressing the gene for human B7-l Ad.hB7 was prepared. Experiments testing its toxicity in mice began and toxicity studies in rhesus monkeys are planned for next year. Significant improvements were made in culture methods for human breast cancer cells from patient samples. The new method utilizes RT-PCR to assess growth factor receptor expression in breast cancer cells thereby permitting the culture media to be individually tailored. Human breast cancer cell lines and fresh patient samples could both be efficiently transduced with the Ad.hB7 expression vector and the B7 protein remained expressed on the cell surface for over one month. A murine mammary adenocarcinoma model was established and characterized from MT-7 derived from a Balbic mouse. The growth of this weakly immunogenic tumor was significantly reduced when the tumor cells were transfected to express B7-l. These results demonstrate that the use of human breast cancer cells for gene therapy studies is feasible, that Ad.hB7 efficiently transduces these breast cancer cells with a high percentage of cells expressing B7 long enough to be used as a vaccine, and finally, that the scientific rationale for this approach is sound as shown in an animal model of breast cancer.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology